1. Field of Invention
The present invention relates to a novel geranylgeranyl diphosphate synthase, process for production thereof, a gene system coding for said enzyme, and a process for producing geranylgeranyl diphosphate using said enzyme.
2. Related Art
Among known isoprenoids (the generic name for substances having the basic skeleton of (C.sub.5 H.sub.8).sub.n) of various chain lengths, geranylgeranyl diphosphate (GGPP) in particular, having a chain length of 20 carbon atoms, is highly valuable in industrial uses as a starting material for terpenoids having various useful physiological activities as well as vitamins A, K and E. Although this GGPP having a high industrial usefulness is manufactured by chemical synthesis, it is extremely expensive due to the extremely low yield.
On the other hand, prenyl transferase is known as an enzyme that synthesizes isoprenoids of various chain lengths using as starting materials, isopentenyl diphosphate (IPP) and allylic diphosphates. Geranylgeranyl diphosphate synthase in particular mainly synthesizes GGPP. Thus, if it was possible to increase the yield of GGPP by using this enzyme reaction, it is expected that GGPP would be able to be manufactured inexpensively. Since by using this enzyme reaction, only the trans-form is synthesized, this enzymatic method is advantageous over chemical synthesis methods in which the cis-form, which is difficult to be separated, is produced as a by-product.
Until now, genes for GGPP synthase (GGPS) were known to be derived from a plant pathogen, Erwinia uredovora, a soil bacterium, Myxococcus xanthus, a red bread mould, Neurospora crassa and so forth. Some of them are expressed in Escherichia coli. However, since none of these enzymes have thermostable, enzyme activity has poor stability. Since these enzymes are unable to be used stably for long periods of time in industrial applications, there has been a need for a more stable enzyme.
GGPP synthase derived from a highly thermophilic bacteria, Sulfolobus acidocardarius, has already been reported in response to this need. Although enzyme derived from Sulfolobus acidocardarius has higher stability than other known enzymes, it has a problem of a low specific activity. In addition, the GGPP synthase derived from a methane-producing bacterium, Methanobacterium thermoautotrophicum, has also been reported as an enzyme having a high thermostability. In this report, the enzyme productivity per cell is so low that it is not practical.
Thus, since there is no geranylgeranyl diphosphate synthase that can be used industrially, the development of a practically useful enzyme is desired.